FKBP1B

Summary

FKBP1B (FKBP prolyl isomerase 1B, HGNC:3712) is a protein-coding gene on chromosome 2p23.3, encoding Peptidyl-prolyl cis-trans isomerase FKBP1B (P68106). Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin.

The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds the immunosuppressants FK506 and rapamycin. It is highly similar to the FK506-binding protein 1A. Its physiological role is thought to be in excitation-contraction coupling in cardiac muscle. There are two alternatively spliced transcript variants of this gene encoding different isoforms.

Source: NCBI Gene 2281 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 123 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3712
Approved symbol	FKBP1B
Name	FKBP prolyl isomerase 1B
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	OTK4, FKBP12.6, PPIase, FKBP9
Ensembl gene	ENSG00000119782
Ensembl biotype	protein_coding
OMIM	600620
Entrez	2281

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000380986, ENST00000380991, ENST00000421839, ENST00000438630, ENST00000452109, ENST00000496149

RefSeq mRNA: 4 — MANE Select: NM_004116 NM_001322963, NM_001322964, NM_004116, NM_054033

CCDS: CCDS1706, CCDS33153, CCDS82423

Canonical transcript exons

ENST00000380986 — 4 exons

Exon	Start	End
ENSE00001630205	24049741	24049886
ENSE00003472153	24060814	24060926
ENSE00003508325	24063064	24063681
ENSE00003648749	24053902	24053949

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2486 / max 203.0264, expressed in 1482 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19169	9.2732	1425
19168	2.9754	1039

Top tissues by expression

133 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.73	gold quality
nucleus accumbens	UBERON:0001882	95.85	gold quality
caudate nucleus	UBERON:0001873	95.51	gold quality
putamen	UBERON:0001874	95.39	gold quality
Ammon’s horn	UBERON:0001954	94.91	gold quality
anterior cingulate cortex	UBERON:0009835	94.76	gold quality
temporal lobe	UBERON:0001871	94.25	gold quality
amygdala	UBERON:0001876	94.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.00	gold quality
right frontal lobe	UBERON:0002810	93.86	gold quality
cerebral cortex	UBERON:0000956	93.71	gold quality
superior frontal gyrus	UBERON:0002661	93.57	gold quality
frontal cortex	UBERON:0001870	93.24	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.23	gold quality
prefrontal cortex	UBERON:0000451	92.90	gold quality
brain	UBERON:0000955	91.89	gold quality
cerebellar cortex	UBERON:0002129	91.55	gold quality
cerebellar hemisphere	UBERON:0002245	91.55	gold quality
cerebellum	UBERON:0002037	91.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.35	gold quality
hypothalamus	UBERON:0001898	91.10	gold quality
duodenum	UBERON:0002114	90.25	gold quality
primary visual cortex	UBERON:0002436	90.05	gold quality
substantia nigra	UBERON:0002038	89.65	gold quality
ganglionic eminence	UBERON:0004023	87.46	gold quality
lower esophagus mucosa	UBERON:0035834	86.50	gold quality
body of stomach	UBERON:0001161	86.49	gold quality
right lung	UBERON:0002167	86.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.69	gold quality
fundus of stomach	UBERON:0001160	84.50	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1307.41
E-HCAD-13	yes	8.56
E-ANND-3	yes	7.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP3

miRNA regulators (miRDB)

37 targeting FKBP1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-7112-3P	97.67	68.77	948

Literature-anchored findings (GeneRIF, showing 23)

• localization of binding site to the NH2-terminal domain of the cardiac Ca2+ release channel (PMID:12446682)
• Data show that VTSIP- and ARVD2-associated point mutations influence positively and negatively, respectively, the binding of RyR2 to its gating protein FKBP12.6. (PMID:12459180)
• data demonstrate that defective regulation of ryanodine receptor 2 causes altered cellular phenotype via profound perturbations in intracellular calcium signaling and highlight a key modulatory role of FK506 binding protein 12.6 (PMID:12754204)
• FKBP1B gene is involved in the genetic susceptibility to the AITDs development in the studied family. (PMID:15497458)
• novel interaction site for FKBP12.6 may be present at the RyR2 C terminus, proximal to the channel pore, a sterically appropriate location that would enable this protein to play a central role in the modulation of this critical ion channel (PMID:15591045)
• FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT. (PMID:15749201)
• Enhancing calstabin binding to ryanodine receptors improves cardiac and skeletal muscle function in heart failure. (PMID:15972811)
• the redox state of the RyR is intimately connected with FKBP binding affinity. (PMID:17200109)
• Data show that K201 abolished spontaneous calcium release in cardiac myocytes, and that treating ventricular myocytes with FK506 to dissociate FKBP12.6 from ryanodine receptor RyR2 did not affect the suppression of spontaneous Ca2+ release by K201. (PMID:17313373)
• Results describe abrupt changes in the expression of FKBP12.6, SERCA2a, PKA, and ECE on reperfusion against ischemia, which are responsible for the rapid occurrence of ventricular fibrillation, and their prevention by CPU86017. (PMID:17506935)
• the loss of FKBP12.6 has no significant effect on the conduction and activation of RyR2 or the propensity for spontaneous Ca(2+) release and stress-induced ventricular arrhythmias (PMID:17921453)
• The findings suggest that FKBP12.6 regulation of RyR2 is unlikely to be the primary defect in inherited arrhythmogenic cardiac disease. (PMID:19226252)
• analysis of the ryanodine receptor FK506-binding protein subunit (PMID:20404344)
• Characterize the kinetics of FKBP12/12.6 binding to RyR2 in ventricular myocytes and effects on calcium signaling. (PMID:20431056)
• FKBP12.6-deficient mice with cardiac hypertrophy do not display exercise-induced arrhythmia and/or sudden cardiac death. (PMID:22087651)
• These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases. (PMID:22236651)
• Sirolimus-FKBP12.6 impairs endothelial barrier function by activation of protein kinase C-alpha and downstream disruption of the p120-VE cadherin interaction in vascular endothelium. (PMID:23887639)
• RyRs have been identified as important targets of FKBP12 and FKBP12.6, members of the immunophilin family (PMID:26009182)
• How phosphorylation of RyR affects channel activity and whether proteins such as the FK-506 binding proteins (FKBP12 and FKBP12.6) are involved in heart failure (PMID:26009186)
• results suggest that both FKBP12.6 and FKBP12 play critical roles in regulating RyR2 function by facilitating the termination of SOICR. (PMID:27154203)
• Total chemical synthesis, refolding, and crystallographic structure of fully active immunophilin calstabin 2 (PMID:27670942)
• Our FRET-based HTS detects RyR binding of accessory proteins calmodulin (CaM) or FKBP12.6…One compound increased FRET and inhibited RyR1, which was only significant at nM [Ca(2+)], and accentuated without CaM present. (PMID:27760856)
• Rieske iron-sulfur protein induces FKBP12.6/RyR2 complex remodeling and subsequent pulmonary hypertension through NF-kappaB/cyclin D1 pathway. (PMID:32669538)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp1b	ENSDARG00000052625
mus_musculus	Fkbp1b	ENSMUSG00000020635
rattus_norvegicus	Fkbp1b	ENSRNOG00000047143
drosophila_melanogaster	Fkbp12	FBGN0013954
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

Paralogs (18): FKBP4 (ENSG00000004478), FKBP6 (ENSG00000077800), FKBP7 (ENSG00000079150), FKBP1A (ENSG00000088832), FKBP5 (ENSG00000096060), FKBP3 (ENSG00000100442), FKBP8 (ENSG00000105701), FKBP14 (ENSG00000106080), FKBP15 (ENSG00000119321), FKBP9 (ENSG00000122642), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase FKBP1B — P68106 (reviewed: P68106)

Alternative names: 12.6 kDa FK506-binding protein, FK506-binding protein 1B, Immunophilin FKBP12.6, Rotamase, h-FKBP-12

All UniProt accessions (4): P68106, F8W6G9, G5E9U6, H7C0Y3

UniProt curated annotations — full annotation on UniProt →

Function. Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Subunit / interactions. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with RYR2.

Subcellular location. Cytoplasm. Sarcoplasmic reticulum.

Tissue specificity. Detected in heart muscle (at protein level). Isoform 1 and isoform 2 are ubiquitous with highest levels in brain and thymus.

Activity regulation. Inhibited by both FK506 and rapamycin.

Similarity. Belongs to the FKBP-type PPIase family. FKBP1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P68106-1	1	yes
P68106-2	2

RefSeq proteins (4): NP_001309892, NP_001309893, NP_004107, NP_473374 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR046357	PPIase_dom_sf	Homologous_superfamily
IPR050689	FKBP-type_PPIase	Family

Pfam: PF00254

Catalyzed reactions (Rhea), 1 shown:

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (15 total): strand 6, turn 4, helix 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

118 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5HKG	X-RAY DIFFRACTION	1.5
4IQ2	X-RAY DIFFRACTION	1.7
4IQC	X-RAY DIFFRACTION	1.9
1C9H	X-RAY DIFFRACTION	2
4C02	X-RAY DIFFRACTION	2.17
7U9X	ELECTRON MICROSCOPY	2.58
7U9T	ELECTRON MICROSCOPY	2.68
7UA5	ELECTRON MICROSCOPY	2.83
8UXC	ELECTRON MICROSCOPY	2.86
9C1E	ELECTRON MICROSCOPY	2.89
7UA4	ELECTRON MICROSCOPY	2.93
7UA3	ELECTRON MICROSCOPY	2.97
8UQ2	ELECTRON MICROSCOPY	2.98
7UA1	ELECTRON MICROSCOPY	2.99
8UXG	ELECTRON MICROSCOPY	3.08
7U9Q	ELECTRON MICROSCOPY	3.11
9OL6	ELECTRON MICROSCOPY	3.11
8UXL	ELECTRON MICROSCOPY	3.12
8UXF	ELECTRON MICROSCOPY	3.13
8UQ3	ELECTRON MICROSCOPY	3.18
9C1F	ELECTRON MICROSCOPY	3.22
9CGQ	ELECTRON MICROSCOPY	3.23
6WOU	ELECTRON MICROSCOPY	3.27
7U9Z	ELECTRON MICROSCOPY	3.29
8UXI	ELECTRON MICROSCOPY	3.29
7VML	ELECTRON MICROSCOPY	3.3
7VMR	ELECTRON MICROSCOPY	3.3
9KDF	ELECTRON MICROSCOPY	3.3
9KDG	ELECTRON MICROSCOPY	3.33
9CGP	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P68106-F1	94.98	0.97

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-5578775	Ion homeostasis

MSigDB gene sets: 434 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_SEQUESTERING_OF_CALCIUM_ION, MULLIGHAN_NPM1_SIGNATURE_3_UP, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION

GO Biological Process (21): ‘de novo’ protein folding (GO:0006458), smooth muscle contraction (GO:0006939), positive regulation of cytosolic calcium ion concentration (GO:0007204), negative regulation of heart rate (GO:0010459), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), neuronal action potential propagation (GO:0019227), calcium-mediated signaling (GO:0019722), insulin secretion involved in cellular response to glucose stimulus (GO:0035773), protein refolding (GO:0042026), T cell proliferation (GO:0042098), negative regulation of calcium-mediated signaling (GO:0050849), release of sequestered calcium ion into cytosol (GO:0051209), negative regulation of release of sequestered calcium ion into cytosol (GO:0051280), obsolete positive regulation of sequestering of calcium ion (GO:0051284), protein maturation (GO:0051604), response to redox state (GO:0051775), negative regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061179), regulation of heart rate (GO:0002027), response to glucose (GO:0009749), insulin secretion (GO:0030073)

GO Molecular Function (8): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), signaling receptor binding (GO:0005102), calcium channel regulator activity (GO:0005246), FK506 binding (GO:0005528), calcium channel inhibitor activity (GO:0019855), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (6): cytoplasm (GO:0005737), membrane (GO:0016020), Z disc (GO:0030018), sarcoplasmic reticulum membrane (GO:0033017), calcium channel complex (GO:0034704), sarcoplasmic reticulum (GO:0016529)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Cardiac conduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein folding	2
regulation of biological quality	2
regulation of release of sequestered calcium ion into cytosol	2
protein binding	2
calcium channel activity	2
muscle contraction	1
regulation of heart rate	1
negative regulation of heart contraction	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
transmission of nerve impulse	1
nervous system process	1
action potential propagation	1
intracellular signaling cassette	1
insulin secretion	1
establishment of localization in cell	1
cellular response to glucose stimulus	1
T cell activation	1
lymphocyte proliferation	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
negative regulation of intracellular signal transduction	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
release of sequestered calcium ion into cytosol	1
negative regulation of calcium ion transmembrane transport	1
gene expression	1
protein metabolic process	1
response to stimulus	1
insulin secretion involved in cellular response to glucose stimulus	1
negative regulation of insulin secretion	1
negative regulation of response to stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
regulation of heart contraction	1
response to hexose	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
ion channel regulator activity	1

Protein interactions and networks

STRING

2301 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP1B	RYR2	Q92736	999
FKBP1B	RYR1	P21817	981
FKBP1B	TRDN	Q13061	963
FKBP1B	CALML3	P27482	935
FKBP1B	CALML5	Q9NZT1	935
FKBP1B	CALML6	Q8TD86	930
FKBP1B	CALML4	Q96GE6	930
FKBP1B	AKAP6	Q13023	929
FKBP1B	ASPH	Q12797	907
FKBP1B	CALM1	P02593	890
FKBP1B	CASQ2	O14958	864
FKBP1B	SH2D3A	Q9BRG2	857
FKBP1B	PRKACA	P17612	846
FKBP1B	PRKACB	P22694	846
FKBP1B	PRKACG	P22612	846

IntAct

34 interactions, top by confidence:

A	B	Type	Score
FKBP1B	RYR2	psi-mi:“MI:2364”(proximity)	0.720
RYR2	FKBP1B	psi-mi:“MI:0915”(physical association)	0.720
FKBP1B	RYR2	psi-mi:“MI:0915”(physical association)	0.720
REL	FKBP1B	psi-mi:“MI:0915”(physical association)	0.560
CAMK2D	FKBP1B	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	KRT31	psi-mi:“MI:0915”(physical association)	0.560
FLJ13057	FKBP1B	psi-mi:“MI:0915”(physical association)	0.560
KRT40	FKBP1B	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	TRIM69	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	REL	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	CAMK2D	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	FKBP1B	psi-mi:“MI:0915”(physical association)	0.560
TRIM69	FKBP1B	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	FLJ13057	psi-mi:“MI:0915”(physical association)	0.560
FKBP1B	RyR1	psi-mi:“MI:0915”(physical association)	0.400
RYR1	FKBP1B	psi-mi:“MI:0915”(physical association)	0.400
FKBP1B	ryr1	psi-mi:“MI:0915”(physical association)	0.400
	FKBP1B	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (38): FKBP1B (Two-hybrid), KRT31 (Two-hybrid), REL (Two-hybrid), ADAMTSL4 (Two-hybrid), GMCL1 (Two-hybrid), KRT40 (Two-hybrid), TRIM69 (Two-hybrid), DDAH2 (Co-fractionation), FKBP1B (Co-fractionation), FKBP1B (Co-fractionation), FKBP1B (Co-fractionation), FKBP1B (Co-fractionation), FKBP1B (Co-fractionation), FKBP1B (Co-fractionation), FKBP1B (Co-fractionation)

ESM2 similar proteins: O04287, O42123, O42993, O94746, P0A0W2, P0A0W3, P0C1J3, P0CP94, P0CP95, P0CY37, P18203, P20080, P20081, P26883, P28725, P28870, P48375, P56989, P62942, P62943, P68106, P68107, P97534, Q13526, Q2U316, Q2UPT7, Q38931, Q43207, Q4HZB8, Q4R383, Q4W9R2, Q4WHX4, Q4WLV6, Q554J3, Q5ATN7, Q5BIN5, Q5VVH2, Q62658, Q6BX45, Q6CF41

Diamond homologs: A5IGB8, G0SC91, O04287, O08437, O42123, O42993, O46638, O94746, O95302, P0A0W2, P0A0W3, P0A9L3, P0A9L4, P0C1B0, P0C1J3, P0C1J5, P0C1J6, P0C1J7, P0CP94, P0CP95, P0CP96, P0CP97, P18203, P20081, P26623, P26884, P26885, P27124, P28870, P30416, P31106, P38911, P44760, P45523, P45878, P48375, P51752, P53605, P54397, P56989

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

123 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2737 predictions. Top by Δscore:

Variant	Effect	Δscore
2:24049883:GACG:G	donor_gain	1.0000
7:32974600:A:AG	acceptor_gain	1.0000
7:32974601:C:G	acceptor_gain	1.0000
7:32974606:T:TA	acceptor_gain	1.0000
7:32974607:G:A	acceptor_gain	1.0000
7:32974756:GGA:G	donor_gain	1.0000
7:32974757:GAG:G	donor_gain	1.0000
7:32974759:GTTT:G	donor_gain	1.0000
7:32974763:G:GG	donor_gain	1.0000
7:32975177:TCTA:T	acceptor_loss	1.0000
7:32975178:CTAG:C	acceptor_loss	1.0000
7:32975179:TAG:T	acceptor_loss	1.0000
7:32975180:A:AG	acceptor_gain	1.0000
7:32975180:AGC:A	acceptor_loss	1.0000
7:32975180:AGCT:A	acceptor_gain	1.0000
7:32975181:G:GG	acceptor_gain	1.0000
7:32975181:GCT:G	acceptor_gain	1.0000
7:32975181:GCTG:G	acceptor_gain	1.0000
7:32975227:T:TA	acceptor_gain	1.0000
7:32975369:GAG:G	donor_gain	1.0000
7:32975370:AG:A	donor_gain	1.0000
7:32975371:GG:G	donor_gain	1.0000
7:32975372:G:GG	donor_gain	1.0000
7:32975372:GTA:G	donor_loss	1.0000
7:32976342:A:AG	acceptor_gain	1.0000
7:32976345:A:AG	acceptor_gain	1.0000
7:32976346:C:G	acceptor_gain	1.0000
7:32976348:TTTCA:T	acceptor_loss	1.0000
7:32976349:TTCAG:T	acceptor_loss	1.0000
7:32976350:TCAG:T	acceptor_loss	1.0000

AlphaMissense

706 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:24060837:T:C	F37L	0.996
2:24060839:T:A	F37L	0.996
2:24060839:T:G	F37L	0.996
2:24060843:T:C	S39P	0.995
2:24060847:C:T	S40F	0.995
2:24063158:T:A	L98H	0.995
2:24063163:T:C	F100L	0.995
2:24063165:T:A	F100L	0.995
2:24063165:T:G	F100L	0.995
2:24060873:T:C	F49L	0.994
2:24060875:C:A	F49L	0.994
2:24060875:C:G	F49L	0.994
2:24063110:C:A	A82E	0.994
2:24063151:G:C	A96P	0.994
2:24063077:A:C	Q71P	0.993
2:24063094:T:C	C77R	0.993
2:24063164:T:C	F100S	0.993
2:24063082:G:C	A73P	0.992
2:24063125:G:A	G87D	0.991
2:24060814:G:A	G29E	0.990
2:24053943:T:C	Y27H	0.989
2:24060838:T:C	F37S	0.989
2:24063158:T:C	L98P	0.989
2:24060907:T:C	F60S	0.988
2:24053914:C:A	P17H	0.987
2:24060841:A:T	D38V	0.987
2:24060847:C:A	S40Y	0.987
2:24060874:T:C	F49S	0.987
2:24060903:G:C	G59R	0.987
2:24060904:G:A	G59D	0.987

dbSNP variants (sampled 300 via entrez): RS1000029386 (2:24036180 T>C), RS1000083777 (2:24043561 T>C), RS1000175357 (2:24055174 A>G), RS1000280823 (2:24061258 A>C), RS1000485936 (2:24035968 C>T), RS1000567815 (2:24062474 C>T), RS1000632747 (2:24061520 G>A,T), RS1000674771 (2:24061779 T>A), RS1000837482 (2:24055797 A>C), RS1000974829 (2:24049931 G>A), RS1001100524 (2:24042754 C>G,T), RS1001177664 (2:24053482 A>G), RS1001182352 (2:24049215 G>T), RS1001250807 (2:24042205 C>G), RS1001289505 (2:24056038 G>A)

Disease associations

OMIM: gene MIM:600620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000337_33	Quantitative traits	6.000000e-06
GCST003837_10	Chronotype	2.000000e-08
GCST005580_274	Intraocular pressure	6.000000e-10
GCST007576_425	Chronotype	2.000000e-12
GCST008163_57	Height	5.000000e-06
GCST009391_1574	Metabolite levels	9.000000e-06
GCST012489_159	Heel bone mineral density x serum urate levels interaction	4.000000e-08
GCST90002385_184	High light scatter reticulocyte count	3.000000e-12
GCST90002386_446	High light scatter reticulocyte percentage of red cells	1.000000e-14
GCST90002405_225	Reticulocyte count	1.000000e-20
GCST90002406_245	Reticulocyte fraction of red cells	4.000000e-18

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004695	intraocular pressure measurement
EFO:0008328	chronotype measurement
EFO:0010516	orotic acid measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2430 (SINGLE PROTEIN), CHEMBL4296662 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 436,213 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL269732	TACROLIMUS ANHYDROUS	4	95,168
CHEMBL413	SIROLIMUS	4	172,798

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

49 potent at pChembl≥5 of 49 total, top 48 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	Kd	0.2	nM	SIROLIMUS
9.42	Kd	0.38	nM	CHEMBL5634031
9.40	Kd	0.4	nM	TACROLIMUS ANHYDROUS
9.22	Kd	0.6	nM	SIROLIMUS
8.91	Ki	1.23	nM	CHEMBL4090599
8.83	Kd	1.49	nM	TACROLIMUS ANHYDROUS
8.52	Ki	3	nM	CHEMBL216520
8.22	Ki	6	nM	CHEMBL2370706
8.22	Ki	6	nM	CYCLOSPORINE
8.22	Ki	6	nM	CHEMBL2370707
8.10	IC50	8	nM	CHEMBL4079746
8.05	Kd	9	nM	CHEMBL4871144
7.72	Kd	19	nM	CHEMBL4878667
7.70	Kd	20	nM	CHEMBL4858532
7.50	Kd	32	nM	CHEMBL4863989
7.48	Ki	33	nM	CHEMBL2370711
7.42	Kd	38	nM	CHEMBL4878890
7.41	Kd	38.9	nM	CHEMBL3623630
7.37	Kd	43	nM	CHEMBL4876415
7.28	Kd	53	nM	CHEMBL4866742
7.21	Kd	62	nM	CHEMBL4872580
7.10	IC50	80	nM	CHEMBL3623630
7.09	Kd	82	nM	CHEMBL4859741
7.07	Kd	85	nM	CHEMBL4856956
7.03	Kd	94	nM	CHEMBL4879078
7.00	Kd	100	nM	CHEMBL4870008
6.98	Kd	105	nM	CHEMBL4862808
6.94	Kd	116	nM	CHEMBL4850434
6.94	Kd	115	nM	CHEMBL4862282
6.69	Kd	203	nM	CHEMBL4876664
6.67	Kd	216	nM	CHEMBL4868302
6.64	Kd	227	nM	CHEMBL4856457
6.64	Kd	227	nM	CHEMBL4850750
6.56	Kd	277	nM	CHEMBL4853042
6.52	Kd	301	nM	CHEMBL4856203
6.47	Kd	335	nM	CHEMBL4855135
6.46	Kd	344	nM	CHEMBL4860544
6.45	Kd	352	nM	CHEMBL4877731
6.42	Kd	383	nM	CHEMBL4863807
6.37	Kd	429	nM	CHEMBL4874574
6.35	Kd	446	nM	CHEMBL4848201
6.30	Kd	495	nM	CHEMBL4863883
6.22	Kd	606	nM	CHEMBL4875870
6.18	Kd	658	nM	CHEMBL4872122
6.15	Kd	715	nM	CHEMBL4866065
6.15	Kd	709	nM	CHEMBL4864747
6.07	Kd	849	nM	CHEMBL4863758
5.97	Kd	1075	nM	CHEMBL4867024

PubChem BioAssay actives

47 with measured affinity, of 59 total; 44 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Sirolimus	1179559: Binding affinity to FKBP12 (unknown origin) by NMR analysis	kd	0.0002	uM
(1R,9S,12S,15S,16E,20E,23R,24S,27R)-1-hydroxy-15,23,27-trimethyl-12-[(2R)-1-[(1S,2S,3S,4R)-2,3,4-trihydroxycyclohexyl]propan-2-yl]-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacosa-16,20-diene-2,3,10,22-tetrone	2139768: Binding affinity to human FKBP12.6 expressed in Escherichia coli BL21 DE3 Gold assessed as dissociation constant incubated for 30 mins by competitive fluorescence polarization assay	kd	0.0004	uM
Tacrolimus	1179559: Binding affinity to FKBP12 (unknown origin) by NMR analysis	kd	0.0004	uM
(1S,5S,6R)-10-(3,5-dichlorophenyl)sulfonyl-5-(methoxymethyl)-3-(pyridin-2-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-2-one	1479800: Displacement of 5-(3-(4-(((5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-5-vinyl-3,10-diazabicyclo[4.3.1]decan-3-yl)methyl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3,10-dihydroanthracen-9-yl)benzoate from human FKBP12.6 after 30 mins by fluorescence polarization assay	ki	0.0012	uM
(3R,6S,8S,9R,14S,15S,17S,20R,27R,29S,30S,32S,33S)-21-ethyl-8,14,17,20,29,32-hexahydroxy-24-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,3,6,10,16,19,25,28,31-nonamethyl-9,15,30,33-tetrakis(2-methylpropyl)-12,27-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,11,23,26-pentone	157232: The compound was tested for inhibition of Peptidyl-propyl isomerase (PPIase).	ki	0.0030	uM
cyclosporine	157232: The compound was tested for inhibition of Peptidyl-propyl isomerase (PPIase).	ki	0.0060	uM
(3R,6S,9R,12S,15R,18R,21S,24S,30S,33S)-15-benzyl-30-ethyl-12-(hydroxymethyl)-33-[(E,1R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,19,25,28-heptamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	157232: The compound was tested for inhibition of Peptidyl-propyl isomerase (PPIase).	ki	0.0060	uM
(3R,6S,9R,12R,15R,18R,21S,24S,27R,30S,33S)-15-benzyl-30-ethyl-33-[(E)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,19,25,27,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	157232: The compound was tested for inhibition of Peptidyl-propyl isomerase (PPIase).	ki	0.0060	uM
2-[4-[9-(6-amino-3-pyridinyl)-2-oxopyrazino[2,3-c]quinolin-1-yl]piperidin-1-yl]acetonitrile	1468099: Inhibition of full length recombinant human mTOR/FKBP12	ic50	0.0080	uM
(2S,9S,12R,20R,21R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0090	uM
(2S,9S,12R,20S,21S)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0190	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10,21-trione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0200	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10,20-trione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0320	uM
(3R,6S,9R,12R,15R,18R,21S,24S,30S,33S)-15-benzyl-30-ethyl-33-[(E,1R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,19,25,28-octamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	157232: The compound was tested for inhibition of Peptidyl-propyl isomerase (PPIase).	ki	0.0330	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10,20-trione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0380	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10,20-trione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0430	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,27,29-hexaene-3,10,21-trione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0530	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,24,26-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0620	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-23,24-dimethoxy-11,18,21-trioxa-4-azatetracyclo[20.3.1.113,17.04,9]heptacosa-1(26),13(27),14,16,22,24-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0820	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-20,21-dihydroxy-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0850	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-24,25-dimethoxy-11,18,22-trioxa-4-azatetracyclo[21.3.1.113,17.04,9]octacosa-1(27),13(28),14,16,23,25-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.0940	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,25,27-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.1000	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,20,27,29-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.1050	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,27,29-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.1150	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,20,25,27-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.1160	uM
[(1R)-3-(3,4-dimethoxyphenyl)-1-(3-methoxyphenyl)propyl] (2S)-1-[(2S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl]piperidine-2-carboxylate	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.2030	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,26-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.3.1.113,17.04,9]nonacosa-1(28),13(29),14,16,20,24,26-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.2160	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-23,26-dimethoxy-11,18,21-trioxa-4-azatetracyclo[20.2.2.113,17.04,9]heptacosa-1(24),13(27),14,16,22,25-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.2270	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,30-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.3.1.113,17.04,9]tritriaconta-1(32),13(33),14,16,28,30-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.2270	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,32-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.2.2.113,17.04,9]tritriaconta-1(30),13(33),14,16,28,31-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.2770	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,29-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.3.1.113,17.04,9]dotriaconta-1(31),13(32),14,16,20,27,29-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.3010	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,32-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.2.2.113,17.04,9]tritriaconta-1(30),13(33),14,16,20,28,31-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.3350	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,31-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.2.2.113,17.04,9]dotriaconta-1(29),13(32),14,16,20,27,30-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.3440	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-29,30-dimethoxy-11,18,23,27-tetraoxa-4-azatetracyclo[26.3.1.113,17.04,9]tritriaconta-1(32),13(33),14,16,20,28,30-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.3520	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,24,27-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.3830	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,31-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.2.2.113,17.04,9]dotriaconta-1(29),13(32),14,16,27,30-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.4290	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-24,27-dimethoxy-11,18,22-trioxa-4-azatetracyclo[21.2.2.113,17.04,9]octacosa-1(25),13(28),14,16,23,26-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.4460	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,29-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.2.2.113,17.04,9]triaconta-1(27),13(30),14,16,20,25,28-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.4950	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,20,24,27-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.6060	uM
(2S,9S,12R,20Z)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-25,28-dimethoxy-11,18,23-trioxa-4-azatetracyclo[22.2.2.113,17.04,9]nonacosa-1(26),13(29),14,16,20,24,27-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.6580	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,27-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.3.1.113,17.04,9]triaconta-1(29),13(30),14,16,20,25,27-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.7090	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-28,31-dimethoxy-11,18,23,26-tetraoxa-4-azatetracyclo[25.2.2.113,17.04,9]dotriaconta-1(29),13(32),14,16,20,27,30-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.7150	uM
(2S,9S,12R)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,29-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.2.2.113,17.04,9]triaconta-1(27),13(30),14,16,25,28-hexaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	0.8490	uM
(2S,9S,12R,20E)-2-cyclohexyl-12-[2-(3,4-dimethoxyphenyl)ethyl]-26,29-dimethoxy-11,18,24-trioxa-4-azatetracyclo[23.2.2.113,17.04,9]triaconta-1(27),13(30),14,16,20,25,28-heptaene-3,10-dione	1775635: Displacement of fluorescent tracer 5-(3-(4-((1S,5S,6S)-10-(3,5-dichlorophenylsulfonyl)-2-oxo-3-(pyridin-3-ylmethyl)-3,10-diazabicyclo[4.3.1]decan-5-yl)-1H-1,2,3-triazol-1-yl)propylcarbamoyl)-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate from recombinant full length C-terminal FLAG-tagged FKBP12.6 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells incubated for 30 mins by fluorescence polarisation competition assay	kd	1.0750	uM

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	increases expression, affects expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression, affects cotreatment	1
trichostatin A	affects expression	1
3,4-dichloroaniline	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
nickel sulfate	decreases expression	1
seocalcitol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Carvedilol	affects binding, increases reaction	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atenolol	affects binding, increases reaction	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	decreases expression, increases reaction	1
Cyclophosphamide	affects response to substance	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3369573	Binding	Binding affinity to FKBP12 (unknown origin) by NMR analysis	Elements and modulation of functional dynamics. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.